We propose to explicate the developmental processes linking adolescent substance abuse to age 29 adult outcomes by completing the in-person longitudinal assessment of 666 male twin pairs and their parents drawn from two population-based cohorts. The older twin cohort, originally seen at age 17 and followed up at ages 20 and 24, has completed the age 29 assessment. The younger cohort, originally recruited at age 11, before the initiation of significant substance use, has completed follow-ups at ages 14, 17, 20, and 24, and will be followed through age 29, with their age 29 assessment enhanced to include new neuropsychological and brain electrocortical measures that were not available for the older cohort at age 29. Data from both cohorts will be combined to examine the developmental trajectories leading to mental health, social, and neurocognitive outcomes evident at age 29. In addition, we will identify factors associated with desistance of substance abuse in early adulthood and determine how desistence ameliorates the negative impact of adolescent-onset abuse on adult outcomes. Our protocol includes a comprehensive longitudinal assessment, including information from multiple informants (parents, teachers, co-twins), that begins in adolescence or earlier for both cohorts. Our developmentally rich data set measures the initiation and progression of tobacco, alcohol, and illicit drug use; externalizing and internalizing psychopathology; biological indices (e.g., brain event-related potentials, resting EEG, measured genes); personality traits; and a wide array of experiential risks (e.g., life-event stress, family and peer relationships, social support, early exposure to substances). We will take advantage of our twin design to examine the contribution of genetic and environmental interplay to the development of adult adjustment, including making use of monozygotic co-twin controls to determine whether environmental differences in risk exposure (including differences in exposure to abused substances) over the course of development are associated with differences in outcome. The completion of this project will provide for a rigorous and comprehensive evaluation of the long-term effects of adolescent-onset substance abuse. PUBLIC HEALTH RELEVANCE: Adolescent substance abuse is a powerful predictor of adult adjustment and mental health, but the mechanisms linking early abuse to later maladjustment are not fully understood. Using twins studied prospectively from age 11 to 29, we will examine how adolescent-onset substance abuse affects the development of mental health in young adulthood.